RATIONAL DOSING OF RANITIDINE(R) IN PEDIATRIC ULCER DISEASE(UD)

Abstract

Dosing requirements for R were determined in 10 children (C) aged 3.5-16 yr with endoscopically proven UD. Gastric acid output (GA) was monitored continuously during the first 2 days of therapy. The therapeutic endpoint was suppression of GA by ⩾90%. C received 0.06mg R/kg over 15 min plus an infusion of 0.02mg R/kg/hr. Each hour they received a bolus of 0.004mg R/kg and the infusion was increased by 0.02mg/kg until the therapeutic endpoint was reached. The infusion was then stopped and serial blood, urine and gastric fluid samples were obtained for the determination of R and GA during the next 12 hr. R was determined by HPLC. These values were used to calculate an IV dose which when administered every 6 hr would suppress GA ⩾90%. On day 2 the calculated dose was given and the monitoring of R pharmacokinetics(PK) and GA were repeated. When C were eating the IV R was crossed over to oral R. Following repeat PK analysis the doses of R were individually adjusted to give a BID dose which would result in an average serum R concentration which suppressed GA ⩾90% in that patient. C were then discharged to receive that dose for 6 wks. The minimum effective serum R concentration was 22.6ng/ml(range 9-65ng/ml). PK analysis revealed (x̄±SD) t½, 1.8(0.2)hr; Vd,2.1(019)4kg; Clp,724.3(163.7) ml/min/1.73m². The absolute bioavailability of R averaged 51%(range 35-95%). Minimal PK differences were observed comparing IV and oral dosing. These data suggest that 1)R is a potent inhibitor of GA in C; 2)C require greater R/kg than adults; 3) oral doses of R should be ≃ twice that of IV.

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